DESCRIPTION: The long-term goal of the proposed work is to develop a new, minimally-invasive treatment of benign uterine disease based on Photodynamic Therapy (PDT). Eventually, uterine PDT may have a significant impact on women's health care and its associated costs because it will provide an inexpensive, outpatient alternative to conventional surgical and medical techniques for treating dysfunctional uterine bleeding (DUB) and improving adenomyosis (AM)-related symptoms. During the past six years we have completed a number of animal, human and modeling studies that have helped us understand the complexity inherent to achieving irreversible endometrial ablation (EA) during PDT. We now propose a major new effort which builds on this foundation and further characterizes how light and drug dosimetry parameters affect clinical outcome. Specific aims include: 1) constructing, characterizing and optimizing performance of a novel, minimally-invasive intrauterine light probe (IULP); 2) completing Phase I/II and beginning Phase III human clinical trials with ALA; 3) testing a limited number of new sensitizers in animal models; and 4) evaluating pharmacokinetics, safety and efficacy of a limited number of new compounds in humans.